title: Development of a simple, fast, and accurate method for the direct quantification of selective estrogen receptor modulators using stable isotope dilution mass spectrometry.
abstract: A rapid analytical procedure was developed to quantify major selective estrogen receptor modulators (SERMs) simultaneously using stable isotope dilution mass spectrometry (SID-LCMS). Two novel isotopically labeled (SIL) analogues of natural SERMs, genistein and daidzein, were synthesized using a H/D exchange reaction mechanism. Computational chemistry coupled with MS and NMR data confirmed the site and mechanism of deuteration. The SIL analogues, which were mono- and dideutero substituted at the ortho positions, exhibited minimal deuterium isotope effects and were stable under the employed sample preparation protocol and MS analysis. An isotopic overlap correction was successfully employed to improve the accuracy and precision of the analytical method. The developed method, which was found to be sensitive, selective, precise and accurate, could be a valuable tool for research focused on determining the bioavailability of individual SERMs.
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota , Saint Paul, Minnesota 55108, United States.
authors.forename: Vamsidhar
authors.initials: V
authors.lastname: Yerramsetty
authors.forename: Mikel
authors.initials: M
authors.lastname: Roe
authors.forename: Jerry
authors.initials: J
authors.lastname: Cohen
authors.forename: Adrian
authors.initials: A
authors.lastname: Hegeman
authors.forename: Baraem
authors.initials: B
authors.lastname: Ismail
mesh_terms: D000818:Animals; D002138:Calibration; D003903:Deuterium; D019833:Genistein / Q000032:analysis / Q000097:blood; D006868:Hydrolysis; D007529:Isoflavones / Q000032:analysis / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008962:Models, Theoretical; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D020845:Selective Estrogen Receptor Modulators / Q000032:analysis*; D012680:Sensitivity and Specificity
chemical_list: D007529:Isoflavones; D020845:Selective Estrogen Receptor Modulators; C004742:daidzein; D003903:Deuterium; D019833:Genistein